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Gene Review

Prkd1  -  protein kinase D1

Mus musculus

Synonyms: PKD, PKD1, Pkcm, Pkd, Prkcm, ...
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Disease relevance of Prkcm


High impact information on Prkcm


Chemical compound and disease context of Prkcm


Biological context of Prkcm


Anatomical context of Prkcm

  • Upon heterologous expression PKDREJ was retained in intracellular membrane compartments and unlike PKD1 did not undergo cleavage in the G-protein-coupled receptor proteolytic site domain (GPS) [15].
  • The cystogenesis of ADPKD is believed to be a monoclonal proliferation of PKD-deficient (PKD(-/-)) renal tubular epithelial cells [16].
  • PKD1/PKCmu promotes alphavbeta3 integrin recycling and delivery to nascent focal adhesions [13].
  • We had found that the activation loop of a PKD mutant, with reduced affinity for diacylglycerol and phorbol esters, was only phosphorylated upon its plasma membrane association [17].
  • COS-7 cells transfected with a PKD cDNA construct (pcDNA3-PKD) exhibit a marked (4.8-fold) increase in [3H]phorbol 12,13-dibutyrate binding [18].

Associations of Prkcm with chemical compounds

  • The bacterially expressed catalytic domain of PKD efficiently phosphorylated the exogenous peptide substrate syntide 2 in serine but did not catalyze significant phosphorylation of a variety of other substrates used by PKCs and other major second messenger regulated kinases [14].
  • A novel protein kinase (named PKD) with an NH2-terminal region containing two cysteine-rich motifs has been expressed in COS-7 cells and identified as a receptor for phorbol esters [18].
  • The substrate specificity of PKD is different from that of previously identified members of the protein kinase C family since it does not efficiently phosphorylate histone III-S, protamine sulfate, or a synthetic peptide based upon the conserved pseudosubstrate region of the protein kinase C family [18].
  • Co-expression studies revealed a pro-proliferative, anti-differentiative effect of PKD on keratinocyte maturation as monitored by increased and decreased promoter activities of keratin 5, a proliferative marker, and involucrin, a differentiative marker, respectively [19].
  • Treatment with pioglitazone improved survival of Pkd1(-/-) embryos and ameliorated the cardiac defects and the degree of renal cystogenesis [1].

Other interactions of Prkcm

  • It is caused by mutations in PKD1 or PKD2, encoding polycystin-1 and -2, which together form a cell surface nonselective cation ion channel [20].
  • The present study focuses on a PKD1 homologue, mouse polycystic kidney disease and receptor for egg jelly (PKDREJ) and its putative role in mammalian fertilization [15].
  • Rapamycin, an inhibitor of mTOR, is highly effective in reducing renal cystogenesis in two independent mouse models of PKD [21].
  • PKD has been the focus of most studies up to date, but little is known about the mechanisms that mediate PKD3 activation [22].
  • We also found that the activation loop phosphorylation and rapid plasma membrane dissociation of PKD were inhibited either by preventing the plasma membrane translocation of PKCepsilon, through abolition of its interaction with receptor for activated C kinase, or by suppressing the expression of PKCepsilon via specific small interfering RNAs [17].

Analytical, diagnostic and therapeutic context of Prkcm


  1. Pioglitazone improves the phenotype and molecular defects of a targeted Pkd1 mutant. Muto, S., Aiba, A., Saito, Y., Nakao, K., Nakamura, K., Tomita, K., Kitamura, T., Kurabayashi, M., Nagai, R., Higashihara, E., Harris, P.C., Katsuki, M., Horie, S. Hum. Mol. Genet. (2002) [Pubmed]
  2. The polycystin 1-C-terminal fragment stimulates ERK-dependent spreading of renal epithelial cells. Joly, D., Ishibe, S., Nickel, C., Yu, Z., Somlo, S., Cantley, L.G. J. Biol. Chem. (2006) [Pubmed]
  3. VEGF receptor 2 blockade leads to renal cyst formation in mice. McGrath-Morrow, S., Cho, C., Molls, R., Burne-Taney, M., Haas, M., Hicklin, D.J., Tuder, R., Rabb, H. Kidney Int. (2006) [Pubmed]
  4. Protein kinase D potentiates DNA synthesis and cell proliferation induced by bombesin, vasopressin, or phorbol esters in Swiss 3T3 cells. Zhukova, E., Sinnett-Smith, J., Rozengurt, E. J. Biol. Chem. (2001) [Pubmed]
  5. PKD1 induces p21(waf1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Bhunia, A.K., Piontek, K., Boletta, A., Liu, L., Qian, F., Xu, P.N., Germino, F.J., Germino, G.G. Cell (2002) [Pubmed]
  6. Somatic inactivation of Pkd2 results in polycystic kidney disease. Wu, G., D'Agati, V., Cai, Y., Markowitz, G., Park, J.H., Reynolds, D.M., Maeda, Y., Le, T.C., Hou, H., Kucherlapati, R., Edelmann, W., Somlo, S. Cell (1998) [Pubmed]
  7. Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease. Torres, V.E., Wang, X., Qian, Q., Somlo, S., Harris, P.C., Gattone, V.H. Nat. Med. (2004) [Pubmed]
  8. Intracellular location and cell context-dependent function of protein kinase D. Marklund, U., Lightfoot, K., Cantrell, D. Immunity (2003) [Pubmed]
  9. Two members of the TRPP family of ion channels, Pkd1l3 and Pkd2l1, are co-expressed in a subset of taste receptor cells. LopezJimenez, N.D., Cavenagh, M.M., Sainz, E., Cruz-Ithier, M.A., Battey, J.F., Sullivan, S.L. J. Neurochem. (2006) [Pubmed]
  10. Lysophosphatidic acid rapidly induces protein kinase D activation through a pertussis toxin-sensitive pathway. Paolucci, L., Sinnett-Smith, J., Rozengurt, E. Am. J. Physiol., Cell Physiol. (2000) [Pubmed]
  11. Protein kinase C-independent activation of protein kinase D is involved in BMP-2-induced activation of stress mitogen-activated protein kinases JNK and p38 and osteoblastic cell differentiation. Lemonnier, J., Ghayor, C., Guicheux, J., Caverzasio, J. J. Biol. Chem. (2004) [Pubmed]
  12. Expression of the protein kinase D (PKD) family during mouse embryogenesis. Oster, H., Abraham, D., Leitges, M. Gene Expr. Patterns (2006) [Pubmed]
  13. PKD1/PKCmu promotes alphavbeta3 integrin recycling and delivery to nascent focal adhesions. Woods, A.J., White, D.P., Caswell, P.T., Norman, J.C. EMBO J. (2004) [Pubmed]
  14. Molecular cloning and characterization of protein kinase D: a target for diacylglycerol and phorbol esters with a distinctive catalytic domain. Valverde, A.M., Sinnett-Smith, J., Van Lint, J., Rozengurt, E. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  15. Polycystic kidney disease and receptor for egg jelly is a plasma membrane protein of mouse sperm head. Butscheid, Y., Chubanov, V., Steger, K., Meyer, D., Dietrich, A., Gudermann, T. Mol. Reprod. Dev. (2006) [Pubmed]
  16. Pkd1 regulates immortalized proliferation of renal tubular epithelial cells through p53 induction and JNK activation. Nishio, S., Hatano, M., Nagata, M., Horie, S., Koike, T., Tokuhisa, T., Mochizuki, T. J. Clin. Invest. (2005) [Pubmed]
  17. G protein-coupled receptor-mediated phosphorylation of the activation loop of protein kinase D: dependence on plasma membrane translocation and protein kinase Cepsilon. Rey, O., Reeve, J.R., Zhukova, E., Sinnett-Smith, J., Rozengurt, E. J. Biol. Chem. (2004) [Pubmed]
  18. Expression and characterization of PKD, a phorbol ester and diacylglycerol-stimulated serine protein kinase. Van Lint, J.V., Sinnett-Smith, J., Rozengurt, E. J. Biol. Chem. (1995) [Pubmed]
  19. Regulation of protein kinase D during differentiation and proliferation of primary mouse keratinocytes. Ernest Dodd, M., Ristich, V.L., Ray, S., Lober, R.M., Bollag, W.B. J. Invest. Dermatol. (2005) [Pubmed]
  20. Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene. Boulter, C., Mulroy, S., Webb, S., Fleming, S., Brindle, K., Sandford, R. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  21. The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Shillingford, J.M., Murcia, N.S., Larson, C.H., Low, S.H., Hedgepeth, R., Brown, N., Flask, C.A., Novick, A.C., Goldfarb, D.A., Kramer-Zucker, A., Walz, G., Piontek, K.B., Germino, G.G., Weimbs, T. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  22. Protein kinase D3 activation and phosphorylation by signaling through G alpha q. Yuan, J., Rey, O., Rozengurt, E. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  23. Characterization of serine 916 as an in vivo autophosphorylation site for protein kinase D/Protein kinase Cmu. Matthews, S.A., Rozengurt, E., Cantrell, D. J. Biol. Chem. (1999) [Pubmed]
  24. Lipid raft disruption triggers protein kinase C and Src-dependent protein kinase D activation and Kidins220 phosphorylation in neuronal cells. Cabrera-Poch, N., Sánchez-Ruiloba, L., Rodríguez-Martínez, M., Iglesias, T. J. Biol. Chem. (2004) [Pubmed]
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